Role of the Yersinia YopJ protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes

Justin L Spinner1, Aaron M Hasenkrug1, Jeffrey G Shannon1

  • 1Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA.

Microbes and Infection
|September 13, 2015
PubMed

Insights

Yersinia pestis virulence factors, specifically YopJ, suppress human immune cells (PMNs) from releasing interleukin-8 (IL-8). This inhibition of IL-8 may delay immune cell recruitment during plague infections.

Area of Science:

  • Immunology
  • Microbiology
  • Bacterial Pathogenesis

Background:

  • Polymorphonuclear leukocytes (PMNs) are crucial for immune responses to infection, producing cytokines that regulate innate and adaptive immunity.
  • Yersinia species are pathogenic bacteria that can cause significant infections, including plague.
  • Cytokine production by PMNs plays a vital role in controlling bacterial infections.

Purpose of the Study:

  • To investigate the cytokine response of human PMNs when incubated with pathogenic Yersinia species.
  • To determine the role of the pCD1 virulence plasmid and its encoded Yop proteins in modulating PMN cytokine production.
  • To identify specific Yop proteins involved in the suppression of interleukin-8 (IL-8) secretion.

Main Methods:

  • Incubation of human PMNs with various Yersinia pestis strains, including wild-type, pCD1-negative, and strains with specific Yop gene deletions.
  • Quantification of cytokine levels, particularly IL-8 (CXCL8), secreted by PMNs using established assays.
  • Comparison of cytokine responses induced by Y. pestis and enteropathogenic Yersinia species.

Main Results:

  • Yersinia pestis strains possessing the pCD1 virulence plasmid significantly inhibited IL-8 production by human PMNs compared to pCD1-negative strains.
  • PMNs incubated with pCD1-negative Y. pestis secreted substantially higher levels of IL-8.
  • Deletion of yopJ in Y. pestis strains restored significant IL-8 production, indicating YopJ's critical role in IL-8 suppression.
  • Enteropathogenic Yersinia species also inhibited IL-8 secretion, with avirulent strains inducing high IL-8 levels.

Conclusions:

  • Virulence plasmid-encoded Yop effectors, particularly YopJ, are responsible for suppressing IL-8 secretion from human PMNs during Yersinia infection.
  • The suppression of the chemotactic IL-8 response by Y. pestis may contribute to the characteristic delayed PMN recruitment observed in bubonic plague.
  • Understanding these immune evasion mechanisms is crucial for developing effective treatments against Yersinia infections.

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